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Rho/Rac of plant (ROP) GTPases are a plant-specific proteins that function as molecular switches, activated by guanine nucleotide exchange factors (GEFs) and inactivated by GTPase-activating proteins (GAPs). The bryophyte Marchantia polymorpha contains single copies of ROP (MpROP), GEFs (ROPGEF and SPIKE (SPK)), and GAPs (ROPGAP and ROP ENHANCER (REN)). MpROP regulates the development of various tissues and organs such as rhizoids, gemmae, and air chambers. While the ROPGEF, KARAPPO (MpKAR) is essential for gemma initiation, the functions of other ROP regulatory factors are less understood. This study focused on two GAPs: MpROPGAP and MpREN. Mpren single mutants showed defects in thallus growth, rhizoid tip growth, gemma development, and air chamber formation, whereas Mpropgap mutants showed no visible abnormalities. However, Mpropgap Mpren double mutants had more severe phenotypes than the Mpren single mutants, suggesting backup roles of MpROPGAP in MpREN-involving processes. Overexpression of MpROPGAP, MpREN resulted in similar gametophyte defects, highlighting the importance of MpROP activation/inactivation cycling (or balancing). Thus, MpREN predominantly, and MpROPGAP as a backup, regulate gametophyte development, most likely by controlling MpROP activation in M. polymorpha.
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PURPOSE: This study aimed to investigate the potential of a newly developed small electrode to accurately record muscle activity during swallowing. MATERIAL AND METHODS: This study included 31 healthy participants. The participants underwent swallowing trials with three types of material. The recordings involved the following conditions: 1) swallowing saliva, 2) swallowing 3 mL water, and 3) swallowing 5 mL water. Two types of electrodes, a conventional electrode (CE) and a newly developed small electrode (NE), were symmetrically positioned on the skin over the suprahyoid muscle group, starting from the center. From the surface electromyography data, the swallowing duration (s), peak amplitude, and rising time (duration from swallowing onset to peak amplitude: s) were measured. Additionally, the equivalence of characteristics of the waveform of muscle activities was calculated by using the variance in both the upper and lower confidence limits in duration and rising time. RESULTS: No significant differences in baseline, swallowing duration or rising time between the CE and NE were observed for any swallowing material. The peak amplitude was significantly higher for the NE than for the CE for all swallowing materials. The CE and NE displayed no significant difference in the equivalence of characteristics of the waveform of muscle activities for any swallowing material. CONCLUSIONS: The gold-plated small electrodes utilized in this study indicated the ability to record the same characteristics of muscle activity as conventional electrodes. Moreover, it was able to capture the muscle activity of each muscle group with improved sensitivity in a narrow area, such as under the submandibular region, with more precision than that of conventional electrodes.
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OBJECTIVE: To compare clinical outcomes of patients treated by female surgeons versus those treated by male surgeons. SUMMARY BACKGROUND DATA: It remains unclear as to whether surgical performance and outcomes differ between female and male surgeons. METHODS: We conducted a meta-analysis to compare patients' clinical outcomes-including patients' postoperative mortality, readmission, and complication rates-between female versus male surgeons. MEDLINE, Embase, CENTRAL, ICTRP, and ClinicalTrials.gov were searched from inception to September 8, 2022. The update search was conducted on July 19, 2023. We used random-effects models to synthesize data and GRADE to evaluate the certainty. RESULTS: A total of 15 retrospective cohort studies provided data on 5,448,121 participants. We found that patients treated by female surgeons experienced a lower post-operative mortality compared with patients treated by male surgeons (8 studies; adjusted odds ratio [aOR], 0.93; 95%CI, 0.88 - 0.97; I2=27%; moderate certainty of the evidence). We found a similar pattern for both elective and non-elective (emergent or urgent) surgeries, although the difference was larger for elective surgeries (test for subgroup difference P=0.003). We found no evidence that female and male surgeons differed for patient readmission (3 studies; aOR, 1.20; 95%CI, 0.83 - 1.74; I2=92%; very low certainty of the evidence) or complication rates (8 studies; aOR, 0.94; 95%CI, 0.88 - 1.01: I2=38%; very low certainty of the evidence). CONCLUSIONS: This systematic review and meta-analysis suggests that patients treated by female surgeons have a lower mortality compared with those treated by male surgeons.
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Hepatocellular carcinoma (HCC) has a high rate of recurrence and poor prognosis, even after curative surgery. Multikinase inhibitors have been applied for HCC patients, but their effect has been restricted. This study aims to clarify the clinical impact of SUV420H1/KMT5B, one of the methyltransferases for histone H4 at lysine 20, and elucidate the novel mechanisms of HCC progression. We retrospectively investigated SUV420H1 expression using HCC clinical tissue samples employing immunohistochemical analysis (n = 350). We then performed loss-of-function analysis of SUV420H1 with cell cycle analysis, migration assay, invasion assay and RNA sequence for Gene Ontology (GO) pathway analysis in vitro, and animal experiments with xenograft mice in vivo. The SUV420H1-high-score group (n = 154) had significantly poorer prognosis for both 5-year overall and 2-year/5-year disease-free survival than the SUV420H1-low-score group (n = 196) (p < 0.001 and p < 0.05, respectively). The SUV420H1-high-score group had pathologically larger tumor size, more tumors, poorer differentiation, and more positive vascular invasion than the SUV420H1-low-score group. Multivariate analysis demonstrated that SUV420H1 high score was the poorest independent factor for overall survival. SUV420H1 knockdown could suppress cell cycle from G1 to S phase and cell invasion. GO pathway analysis showed that SUV420H1 contributed to cell proliferation, cell invasion, and/or metastasis. Overexpression of SUV420H1 clinically contributed to poor prognosis in HCC, and the inhibition of SUV420H1 could repress tumor progression and invasion both in vitro and in vivo; thus, further analyses of SUV420H1 are necessary for the discovery of future molecularly targeted drugs.
Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Animals , Humans , Mice , Carcinoma, Hepatocellular/pathology , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , Gene Expression Regulation, Neoplastic , Histone Methyltransferases/genetics , Histone Methyltransferases/metabolism , Liver Neoplasms/pathology , Methyltransferases/genetics , Prognosis , Retrospective StudiesABSTRACT
OBJECTIVES: To investigate the impact of no cost sharing on paediatric care on usage and health outcomes, and whether the effect varies by household income levels. DESIGN: Regression discontinuity design. SETTING: Nationwide medical claims database in Japan. PARTICIPANTS: Children aged younger than 20 years from April 2018 to March 2022. EXPOSURE: Co-insurance rate that increases sharply from 0% to 30% at a certain age threshold (the threshold age varies between 6 and 20 years depending on region). PRIMARY OUTCOME MEASURES: The outpatient care usage (outpatient visit days and healthcare spending for outpatient care) and inpatient care (experience of any hospitalisation and healthcare spending for inpatient care). RESULTS: Of 244 549 children, 49 556 participants were in the bandwidth and thus included in our analyses. Results from the regression discontinuity analysis indicate that no cost sharing was associated with a significant increase in the number of outpatient visit days (+5.26 days; 95% CI, +4.89 to +5.82; p<0.01; estimated arc price elasticity, -0.45) and in outpatient healthcare spending (+US$369; 95% CI, +US$344 to +US$406; p<0.01; arc price elasticity, -0.55). We found no evidence that no cost sharing was associated with changes in inpatient care usage. Notably, the effect of no cost-sharing policy on outpatient healthcare usage was larger among children from high-income households (visit days +5.96 days; 95% CI, +4.88 to +7.64, spending +US$511; 95% CI, +US$440 to +US$627) compared with children from low-income households (visit days +2.64 days; 95% CI, +1.54 to +4.23, spending +US$154; 95% CI, +US$80 to +US$249). CONCLUSIONS: No cost sharing for paediatric care was associated with a greater usage of outpatient care services, but did not affect inpatient care usage. The study found that this effect was more pronounced among children from high-income households, indicating that the no cost sharing disproportionately benefits high-income households and may contribute to larger disparities.
Subject(s)
Ambulatory Care , Cost Sharing , Child , Humans , Databases, Factual , Elasticity , Health FacilitiesABSTRACT
This cross-sectional study aimed to examine the relationships between lip seal strength, tongue pressure, and daytime sleepiness in Japanese workers. A self-administered questionnaire which comprised the Epworth Sleepiness Scale (ESS) was completed by 496 workers, and excessive daytime sleepiness was defined by an ESS score of 11 or over. Lip seal strength and tongue pressure were measured in all participants, and multiple regression analyses were performed to examine the effects of lip seal strength and tongue pressure on daytime sleepiness. The median ESS score was 5.0 (25th and 75th percentiles: 2.0 and 8.0), and 42 (8.5%) workers had excessive daytime sleepiness. The median lip seal strength was 13.5 N (11.4, 16.3), and the tongue pressure was 41.7 kPa (35.2, 48.3). Workers with higher ESS scores had significantly lower levels of lip seal strength than those without, following adjustments for age and body mass index (BMI) values (ß (95% confidence interval): -0.043 [-0.081, -0.004]). However, tongue pressure was not significantly associated with ESS score after adjustments for age and/or BMI. These results suggest that maintaining moderate lip seal strength may help prevent excessive daytime sleepiness in Japanese workers regardless of age or BMI.
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The objective of the current study was to elucidate the clinicopathological significance and appearance of in vitro three-dimension (3D) spheroid models of oral malignant tumors that were prepared from four pathologically different squamous cell carcinoma (OSCC; low-grade; SSYP and MO-1000, intermediate-grade; LEM2) and oral adenosquamous carcinoma (OASC; high-grade; Mesimo) obtained from patients with different malignant stages. To characterize the biological significance of these cell lines themselves, two-dimensional (2D) cultured cells were subjected to cellular metabolic analysis by a Seahorse bioanalyzer alongside the measurement of the cytotoxicity of cisplatin (CDDP). The appearance of their 3D spheroids was then observed by phase contrast microscopy, and both 2D and 3D cultured cells were subject to trypsin digestion and qPCR analysis of factors related to oncogenic signaling and other related analyses. ATP-linked respiration and proton leaking were significantly different among the four cell lines, and the malignant stages of these cultures were significantly associated with increased ATP-linked respiration and decreased proton leakage. Alternatively, the appearances of these 3D spheroids were also significantly diverse among them, and their differences increased in the order of LEM2, MO-1000, SSYP, and Mesimo. Interestingly, these orders were exactly the same in that the efficacies of CDDP-induced cytotoxicity increased in the same order. qPCR analysis indicated that the levels of expression of oncogenic signaling-related factors varied among these four cell lines, and the values for fibronectin and a key regulator of mitochondrial biogenesis, PGC-1α, were prominently elevated in cultures of the worst malignant Mesimo cells. In addition, although 0.25% trypsin-induced destruction was comparable among all four 2D cultured cells, the values for the 3D spheroids were also substantially varied among these cultures. The findings reported herein indicate that cellular metabolic functions and 3D spheroid architectures may be valuable and useful indicators for estimating the pathological and drug-sensitive aspects of OSCC and OASC malignancies.
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Totally implantable venous access ports (TIVAPs) are widely used for chemotherapy and other purposes in patients with cancer. Their convenience and safety make them ideal for long-term use. However, sometimes there are cases in which TIVAPs remain in the vessel following the completion of long-term chemotherapy and are difficult to remove due to the adhesion of the catheter to the vessel wall. In this study, we encountered a case in which a TIVAP catheter adhering to a blood vessel was fractured during removal and the catheter left in the vessel could not be retrieved by a snare because it had no free end. Finally, the catheter was successfully removed using a peel-away sheath. No complications or residual catheters were associated with the removal procedure.
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An increase in households with food insecurity has been reported during the COVID-19 pandemic, but the trend of food insecurity during the pandemic remains unclear. Using Household Pulse Survey (HPS) data over 34 weeks from June 2020 to September 2021 (nationally representative samples of US adults in the households from the US Census Bureau), we examined racial disparity and trends of food scarcity amid the COVID-19 pandemic. The time series plots illustrated that the food scarcity rate was incremental until December 2020 and began improving thereafter across all racial groups. Such improvements in food scarcity were accompanied by the rise in regular income rates while the use of food assistance programs, unemployment insurance, and stimulus payments remained unchanged or reduced. As the US economy recovered, the gaps in food scarcity rates also narrowed between Black/Hispanic and White households.
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Lip seal strength and tongue pressure are related to sarcopenia in older adults and are directly linked to the quality of life of workers after retirement. This study examined lip seal strength and tongue pressure among Japanese male workers by age. A self-administered questionnaire survey including alcohol consumption and smoking was conducted on 454 male workers. Height, weight, lip seal strength, and tongue pressure were also measured and then stratified by age (20s, 30s, 40s, 50s, and 60s and over). The mean (25th, 75th percentiles) lip seal strength and tongue pressure for all workers were 13.7 N (11.6, 16.4) and 41.7 kPa (35.2, 48.2), respectively. Both lip seal strength and tongue pressure were lowest in the 20s, at 12.1 N (9.6, 14.0) and 40.6 kPa (33.4, 47.6), respectively. The multiple regression analysis adjusted for smoking showed a significant positive association between lip seal strength and BMI for the 20s, 50s, and 60s and over, and a significant positive association between tongue pressure and BMI for the 30s, 40s, 50s, and 60s and over. To maintain oral health in older adults, it may be useful to measure workers' lip seal strength and tongue pressure and intervene at an earlier stage.
Subject(s)
Lip , Tongue , Aged , Humans , Male , East Asian People , Pressure , Quality of Life , SarcopeniaABSTRACT
Auxin plays pleiotropic roles in plant development via gene regulation upon its perception by the receptors TRANSPORT INHIBITOR RESPONSE 1/AUXIN SIGNALING F-BOX (TIR1/AFBs). This auxin-regulated transcriptional control mechanism originated in the common ancestor of land plants. Although the complete loss of TIR1/AFBs causes embryonic lethality in Arabidopsis thaliana, it is unclear whether the requirement for TIR1-mediated auxin perception in cell viability can be generalized. The model liverwort Marchantia polymorpha has a minimal auxin signaling system with only a single TIR1/AFB, MpTIR1. Here we show by genetic, biochemical, and transcriptomic analyses that MpTIR1 functions as an evolutionarily conserved auxin receptor. Null mutants and conditionally knocked-out mutants of MpTIR1 were viable but incapable of forming any organs and grew as cell masses. Principal component analysis performed using transcriptomes at various developmental stages indicated that MpTIR1 is involved in the developmental transition from spores to organized thalli, during which apical notches containing stem cells are established. In Mptir1 cells, stem cell- and differentiation-related genes were up- and downregulated, respectively. Our findings suggest that, in M. polymorpha, auxin signaling is dispensable for cell division but is essential for three-dimensional patterning of the plant body by establishing pluripotent stem cells for organogenesis, a derived trait of land plants.
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Cell Survival , Indoleacetic Acids , Marchantia , Gene Expression Regulation, Plant/genetics , Indoleacetic Acids/pharmacology , Marchantia/geneticsABSTRACT
Immune checkpoint inhibitor-based cancer immunotherapy has provided an additional therapeutic option for oral squamous cell carcinoma (OSCC) with recurrence or distant metastases. However, further improvement of OSCC treatment is required to develop the optimal combination or order for chemoradiotherapy and immunotherapy. Along with the accumulation of clinical knowledge and evidence, it is also essential to clarify the biological impact of chemo-radiotherapeutic agents on the cancer immune microenvironment. In this study, we investigated the effects of cisplatin (CDDP), a key therapeutic agent for OSCC, on programmed death-ligand 1 (PD-L1) expression in OSCC lines. Although CDDP treatment increased the surface levels of PD-L1 on OSCC cell lines, the gene and total protein expression levels of PD-L1 were not altered. We also demonstrated that the phosphorylation of heat shock factor 1 and heat shock protein 90 was involved in this process. In addition, CDDP-induced PD-L1 attenuated the target-specific cytotoxic T lymphocyte reaction to OSCC. These results provide an immunobiological basis for the response of OSCC to CDDP and will contribute to our biological understanding of the action of novel combination therapy including immunotherapy together with platinum-based chemotherapy for OSCC.
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Carcinoma, Squamous Cell , Head and Neck Neoplasms , Mouth Neoplasms , Humans , Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/genetics , Squamous Cell Carcinoma of Head and Neck , B7-H1 Antigen/metabolism , Cisplatin/pharmacology , Cisplatin/therapeutic use , Mouth Neoplasms/drug therapy , Mouth Neoplasms/genetics , Mouth Neoplasms/metabolism , Tumor MicroenvironmentABSTRACT
Cytokinin, a plant hormone, plays essential roles in organ growth and development. The type-B response regulator-mediated cytokinin signaling is repressed by type-A response regulators and is conserved in the liverwort Marchantia polymorpha. Its signal coordinates the development of diverse organs on the thallus body, such as the gemma cup, rhizoid, and air pores. Here we report that the type-B response regulator MpRRB upregulates the expression of the R2R3-MYB transcription factor GEMMA CUP-ASSOCIATED MYB1 (MpGCAM1) in M. polymorpha. Whereas both Mpgcam1 and Mprrb knockout mutants exhibited defects in gemma cup formation, the Mpgcam1 Mprra double mutant, in which cytokinin signaling is activated due to the lack of type-A response regulator, also formed no gemma cups. This suggests that MpGCAM1 functions downstream of cytokinin signaling. Inducible overexpression of MpGCAM1 produced undifferentiated cell clumps on the thalli of both wild-type and Mprrb. However, smaller thalli were formed in Mprrb compared to the wild-type after the cessation of overexpression. These results suggest that cytokinin signaling promotes gemma cup formation and cellular reprogramming through MpGCAM1, while cytokinin signals also participate in activating cell division during thallus development.
Subject(s)
Cytokinins , Marchantia , Marchantia/genetics , Transcription Factors/geneticsABSTRACT
Anorectal bleeding is the second most common site of lower gastrointestinal bleeding. Colonoscopy remains the gold standard test to localize sources of lower gastrointestinal bleeding, but it can miss left-sided colon pathologies such as diverticula, rectal varices, and internal hemorrhoids. We report an unusual case of a male cirrhotic patient with massive hemorrhoidal bleeding which went undiagnosed despite multiple imaging and endoscopic evaluations. He underwent urgent sigmoidoscopy that identified grade III internal hemorrhoids and sclerotherapy which resolved the hematochezia. Decompensated cirrhosis complicates patient candidacy for surgical hemorrhoidectomy, but sclerotherapy is a viable option even for high-risk patients. Urgent sigmoidoscopy during active bleeding should be considered if hemorrhoidal bleeding is suspected but inconclusive by colonoscopy.
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BACKGROUND: Persistent descending mesocolon, an anomaly of fixation of the mesentery of the descending colon, can sometimes cause complications such as intestinal obstruction and intussusception. We present the first reported case of sigmoid volvulus with persistent descending mesocolon. CASE PRESENTATION: An 82-year-old Japanese man had intermittent lower abdominal pain. Abdominal computed tomography showed dilation and a shift to the right side of the sigmoid colon, but no findings of volvulus. The next day, he presented continuous lower abdominal pain with bloody stool. A second abdominal computed tomography showed strangulation and dilation of the sigmoid colon, with shift from the right side of the abdominal cavity to the pelvic space. This suggested the descending colon was running to the medial side with sigmoid volvulus. Emergency surgery was performed for volvulus with persistent descending mesocolon. Operative findings revealed dilation of the sigmoid colon with a partial poorly colored region and strangulation that caused volvulus. After releasing the strangulation of the sigmoid colon, the descending colon was revealed to be running more to the medial side, with adherence to small intestinal mesentery. There was no Toldt's fusion fascia at the descending colon. Persistent descending mesocolon was therefore diagnosed due to abnormality of fixation of the descending colon. The sigmoid colon, including the poorly colored region, was resected and reconstructed, while the inferior mesenteric and left colonic arteries were preserved because of the complexity of the vascular system running around the descending and sigmoid colon due to the shortened mesentery. These findings were pathologically compatible with circulatory compromise and intestinal degeneration due to sigmoid volvulus. The patient had no complications after discharge, including in relation to defecation. CONCLUSION: Persistent descending mesocolon can occasionally cause acute abdominal symptoms requiring immediate treatment. A computed tomography finding of the descending colon running more to the medial side than ordinary cases can aid diagnosis of persistent descending mesocolon.
Subject(s)
Abdomen, Acute , Intestinal Volvulus , Laparoscopy , Mesocolon , Abdominal Pain/etiology , Abdominal Pain/surgery , Aged, 80 and over , Colon, Sigmoid/diagnostic imaging , Colon, Sigmoid/surgery , Humans , Intestinal Volvulus/diagnosis , Intestinal Volvulus/diagnostic imaging , Laparoscopy/methods , Male , Mesocolon/abnormalities , Mesocolon/diagnostic imaging , Mesocolon/surgeryABSTRACT
Purpose: To evaluate the feasibility and safety of transarterial injection of a miriplatin-iodized oil suspension combined with Emprint miriplatin-iodized oil suspension-microwave ablation in patients with medium-sized (3-5 cm) hepatocellular carcinomas. Materials and Methods: This retrospective study included a total of 11 patients with 12 hepatocellular carcinomas (mean size, 3.6 ± 0.6 cm) underwent miriplatin-iodized oil suspension-microwave ablation. Microwave ablation was performed under the guidance of computed tomography fluoroscopy following transarterial miriplatin-iodized oil suspension injection on the same day. Technical success, complications, and local tumor progression were assessed. Results: The primary and secondary technical success rates were 75.0% and 100%, respectively. The number of treatment sessions per nodule was 1.25 ± 0.45. A total 15 sessions were required to achieve technical success (one session in nine lesions, two sessions in three lesions). Two major complications (pneumothorax [n = 1] and hemorrhage [n = 1]) occurred (2/15, 13.3%). No local tumor progression was observed during the follow-up period (mean 12.0 ± 2.0 months, range 2.7-23.9 months). Conclusions: Miriplatin-iodized oil suspension-microwave ablation for medium-sized hepatocellular carcinomas can be safely performed with good local control.
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Phytohormone abscisic acid (ABA) plays a key role in stomata closure, osmostress acclimation, and vegetative and embryonic dormancy. Group B3 Raf protein kinases (B3-Rafs) serve as positive regulators of ABA and osmostress signaling in the moss Physcomitrium patens and the angiosperm Arabidopsis thaliana. While P. patens has a single B3-Raf called ARK, specific members of B3-Rafs among six paralogs regulate ABA and osmostress signaling in A. thaliana, indicating functional diversification of B3-Rafs in angiosperms. However, we found that the liverwort Marchantia polymorpha, belonging to another class of bryophytes, has three paralogs of B3-Rafs, MpARK1, MpARK2, and MpARK3, with structural variations in the regulatory domains of the polypeptides. By reporter assays of the P. patens ark line and analysis of genome-editing lines of M. polymorpha, we found that these B3-Rafs are functionally redundant in ABA response, with respect to inhibition of growth, tolerance to desiccation and expression of stress-associated transcripts, the majority of which are under the control of the PYR/PYL/RCAR-like receptor MpPYL1. Interestingly, gemmae in gemma cups were germinating only in mutant lines associated with MpARK1, indicating that dormancy in the gametophyte is controlled by a specific B3-Raf paralog. These results indicated not only conservation of the role of B3-Rafs in ABA and osmostress response in liverworts but also functional diversification of B3-Rafs, which is likely to have occurred in the early stages of land plant evolution.
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The liverwort Marchantia polymorpha has been utilized as a model for biological studies since the 18th century. In the past few decades, there has been a Renaissance in its utilization in genomic and genetic approaches to investigating physiological, developmental, and evolutionary aspects of land plant biology. The reasons for its adoption are similar to those of other genetic models, e.g. simple cultivation, ready access via its worldwide distribution, ease of crossing, facile genetics, and more recently, efficient transformation, genome editing, and genomic resources. The haploid gametophyte dominant life cycle of M. polymorpha is conducive to forward genetic approaches. The lack of ancient whole-genome duplications within liverworts facilitates reverse genetic approaches, and possibly related to this genomic stability, liverworts possess sex chromosomes that evolved in the ancestral liverwort. As a representative of one of the three bryophyte lineages, its phylogenetic position allows comparative approaches to provide insights into ancestral land plants. Given the karyotype and genome stability within liverworts, the resources developed for M. polymorpha have facilitated the development of related species as models for biological processes lacking in M. polymorpha.